Non-Hodgkin's lymphoma (NHL) incidence has increased dramatically in recent decades in the U.S. and worldwide. While this escalation has been considered almost epidemic in scope, the etiology of most subtypes of this heterogeneous group of malignancies remains elusive. Development of effective prevention and treatment strategies are highly unlikely without the identification of etiologic factors that contribute to development of this malignancy. The presence of simian virus 40 (SV40) has been reported in several human tumors, but the most common of these is NHL. Given existing evidence linking some specific subtypes of NHL to viral etiologies, a systematic and comprehensive assessment of the potential role of this virus in lymphomagenesis is warranted. The aims of this study are: to determine the prevalence of SV40 in tumors of B-cell origin as compared to normal lymph node specimens using sensitive, standardized detection techniques; to evaluate the role of SV-40 in lymphomagenesis; and to develop/optimize specific serologic tests for addressing viral transmissibility within familial clusters. This study will provide a comprehensive and objective assessment of the potential role of this virus in NHL. Regardless of the findings, this study will increase knowledge that will contribute to our understanding of the broader role of infectious pathogens in lymphoma. This will be the first study that addresses the potential association between SV40 and NHL with intentional recruitment of a representative sample of subjects (N=300) who undergo a comprehensive epidemiologic assessment, acquisition of specimens in a standardized fashion, and provision of evidence of tumorigenesis and complementary prevalence of antibody positivity. As demonstrated with other virally- induced tumors, such a conclusion would afford diverse opportunities for NHL prevention strategies specific to SV40 infection, i.e. vaccines (primary) or pharmacology therapy (secondary), and cancer control (tertiary), i.e. antiviral therapy or virus-targeted immunotherapy. [unreadable] [unreadable] [unreadable]